Meloche J L, Smith T K
Department of Nutritional Sciences, University of Guelph, Ontario, Canada.
Proc Soc Exp Biol Med. 1995 Dec;210(3):260-5. doi: 10.3181/00379727-210-43947.
T-2 toxin is a Fusarium trichothecene mycotoxin that has been shown to alter brain neurochemistry and eating behavior in animals eating contaminated diets. Experiments were conducted to determine the role of altered tissue amino acid metabolism in the etiology of acute T-2 toxicosis. Fasted weanling rats were orally dosed with 0 or 2.0 mg T-2 toxin/kg body weight. Blood, brain, liver, and muscle tissue were excised 4 and 8 hr after dosing, and amino acid concentrations were determined. Hepatic enlargement coupled with reduced liver concentrations of free small neutral, large neutral, and basic amino acids were seen 4 hr after dosing. Brain and muscle amino acid concentrations were largely refractory to treatment, while the plasma concentrations of tyrosine and lysine, and the sum of the basic amino acids fell. Hepatic amino acid concentrations returned to control levels 8 hr after dosing at which time aminoacidemia was seen. This was due partially to an increase in plasma concentrations of large neutral amino acids including particularly the branched-chain amino acids. A subsequent experiment was conducted to determine the effect of T-2 toxin on 14C-leucine uptake and incorporation into protein in liver slices 4 hr after dosing. Exposure to T-2 toxin reduced total (free + protein-bound) uptake of leucine due primarily to reduced incorporation of leucine into newly-synthesized hepatic protein. It was concluded that reduced amino acid uptake by liver preceded aminoacidemia in acute T-2 toxicosis, although it is not clear how this might influence subsequent changes in brain neurochemistry and behavior.
T-2毒素是一种镰刀菌单端孢霉烯族霉菌毒素，已证实它会改变食用受污染日粮动物的大脑神经化学和进食行为。开展实验以确定组织氨基酸代谢改变在急性T-2中毒病因学中的作用。对禁食的断乳大鼠经口给予0或2.0毫克T-2毒素/千克体重。给药后4小时和8小时切除血液、大脑、肝脏和肌肉组织，并测定氨基酸浓度。给药后4小时可见肝脏肿大，同时肝脏中游离小中性氨基酸、大中性氨基酸和碱性氨基酸的浓度降低。大脑和肌肉中的氨基酸浓度在很大程度上对治疗不敏感，而血浆中酪氨酸和赖氨酸的浓度以及碱性氨基酸的总和下降。给药后8小时肝脏氨基酸浓度恢复到对照水平，此时出现氨基酸血症。这部分是由于包括支链氨基酸在内的大中性氨基酸的血浆浓度增加。随后进行了一项实验，以确定给药后4小时T-2毒素对肝切片中14C-亮氨酸摄取和掺入蛋白质的影响。暴露于T-2毒素会降低亮氨酸的总（游离+蛋白质结合）摄取，这主要是由于亮氨酸掺入新合成的肝脏蛋白质中的量减少。得出的结论是，在急性T-2中毒中，肝脏氨基酸摄取减少先于氨基酸血症，尽管尚不清楚这如何可能影响随后大脑神经化学和行为的变化。
